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FLASH GENE
Symbol ZFHX3 contributors: mct/npt - updated : 20-09-2016
HGNC name zinc finger homeobox 3
HGNC id 777
Location 16q22.2      Physical location : 72.816.787 - 73.092.534
Genatlas name see TSG16B
Synonym name
  • alpha fetoprotein enhancer binding protein
  • AT-binding transcription factor 1
  • AT motif-binding factor 1
  • Synonym symbol(s) ATBF1, ZFH-3, ATBT, ZNF927
    DNA
    TYPE functioning gene
    STRUCTURE 275.75 kb     10 Exon(s)
    regulatory sequence Promoter
    Binding site   hormone
    text structure
  • a CCG repeat in 5'utr of ATBF1-B
  • estrogen up-regulated the transcription of ZFHX3, which was mediated by the direct binding of the ESR1 onto the ZFHX3 promoter
  • MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    10 splicing initiation site 16064 404 3703 - 2011 21367855
  • also called ATBF1 - variant A, isoform a
  • 920 AA extension at the N terminus skipping exons 2 and 3, ATPase activity, DNA/RNA dependent
  • activated during neuronal differentiation
  • - splicing initiation site 12778 306 2789 - 2011 21367855
  • also called ATBF1 - variant B, isoform b
  • starting from exon 2
  • - - 7800 306 2296 - 2011 21367855
  • also called MAB4A11 (SRMB00)
  • splicing coactivator liking the RNA recognition motifs
  • - - - 160 - - 2011 21367855
    also called MAB1C8 (SRM160)
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivesalivary gland   highly
    Hearing/Equilibriumear   highly
    Nervousbrain   highly Homo sapiensFetal
    Reproductivefemale systembreastmammary gland highly Homo sapiens
    Visualeye   highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo, neonatal, pregnancy
    Text brain
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • four helix-turn-helix (homeo) domains
  • 23 zinc finger motifs
  • multiple putative nuclear receptor boxes, including one consensus LXXLL motif and 31 of its variants LXXXL
  • one DEAD and one DEAH boxes (Asp-Glu-Ala-Asp/His)
  • a RNA and an ATP binding sites
  • two large RS domains and many phosphorylation sites
  • HOMOLOGY
    interspecies homolog to Drosophila ZFH-2
    homolog to murine Atbf1
    ortholog to C.elegans zc123.3
    Homologene
    FAMILY
  • giant, multiple-homeodomain and zinc finger family
  • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,nucleus,chromatin/chromosome
    text
  • normally localized in the nucleus, but is often mislocalized in the cytoplasm in cancer cells
  • basic FUNCTION
  • AT-binding transcription factor 1 and DNA/RNA dependent ATPase activity, maybe involved in neuronal differentiation (ATBF1-A)
  • regulatory factor for STAT3-mediated signal transduction through its interaction with PIAS3
  • regulating myoblastic differentiation
  • plays a role in both the maintenance of breast epithelial homeostasis and breast tumorigenesis caused by elevated estrogen levels
  • inhibits estrogen-mediated cell proliferation and gene regulation in ER-positive breast cancer cells by selectively competing for binding to the ESR1 with NCOA3
  • may have an autoregulatory feedback loop with estrogen-ESR1 signaling
  • appears to be the first gene that has an autoregulatory negative feedback loop with estrogen-ESR1 signaling
  • transcription factor that regulates genes responsible for repairing tissues and the protection of cells from oxidative stress
  • plays a role in the development of pubertal mammary gland likely by modulating the function of estrogen-ER signaling in luminal cells and by modulating gene expression in basal cells
  • nuclear localization and SUMOylation are important for the transcription factor function of ZFHX3, and ZFHX3 could cooperate with promyelocytic leukemia (PML)-nuclear body to regulate protein SUMOylation in different biological processes
  • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA an AT-rich motif in the alpha-fetoprotein gene enhancer
    RNA
    small molecule metal binding, nucleotide,
  • Zn2+
  • ATP
  • protein
  • interacting with v-Myb in regulation of its transactivation
  • interacting with PIAS3
  • required for the PIT1 gene early activation
  • associates with RUNX3 and translocates to the nucleus in response to TGF-beta signal transduction and might function in the nucleus as tumor suppressor and transcriptional regulator
  • estrogen induces the binding of the ESR1 onto the promoter of ZFHX3 and ZFHX3 is an ESR1 target gene
  • TRIM25 is an E3 ubiquitin ligase mediating oestrogen-induced ZFHX3 protein degradation
  • because of its ability to suppress AFP gene transcription in hepatic cells, ZFHX3 is a factor associated with differentiation of the hepatocyte
  • phosphorylation of ZFHX3 was an important regulatory mechanism protecting it from digestion by CAPN1
  • is a transcriptional target of Progesterone-PGR signaling in mammary epithelial cells
  • cell & other
    REGULATION
    activated by progesterone (PG)(its expression is upregulated by PG via the binding of PGR to the ZFHX3 promoter, and ZFHX3 is necessary for PG to induce the expression of stem cell markers and the expansion of progenitor cells
    Other higher levels of estrogen cause the degradation of ZFHX3 protein by the proteasome system
    phosphorylation of ZFHX3 is a key mechanism for the protection of ZFHX3 from degradation
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral somatic mutation      
    in prostate cancer
    tumoral     --low  
    in breast cancers with poor prognosis
    Susceptibility
  • to atrial fibrillation (AF)
  • to Kawasaki disease (KD)
  • Variant & Polymorphism SNP
  • rs7193343-T, associated significantly with AF
  • rs7199343 significantly associated to KS (Burgner 2009)
  • rs2106261 in ZFHX3 confers a significant risk of AF in a Chinese Han population
  • Candidate gene
  • ZFHX3, MACF1, RBM15, and SETD2 are Orofacial cleft candidate risk genes
  • Marker
    Therapy target
    ANIMAL & CELL MODELS